Proposed solutions to anthropogenic climate change: A systematic literature review and a new way forward.

Humanity is now facing what may be the biggest challenge to its existence: irreversible climate change brought about by human activity. Our planet is in a state of emergency, and we only have a short window of time (7-8 years) to enact meaningful change. The goal of this systematic literature review is to summarize the peer-reviewed literature on proposed solutions to climate change in the last 20 years (2002-2022), and to propose a framework for a unified approach to solving this climate change crisis. Solutions reviewed include a transition toward use of renewable energy resources, reduced energy consumption, rethinking the global transport sector, and nature-based solutions. This review highlights one of the most important but overlooked pieces in the puzzle of solving the climate change problem - the gradual shift to a plant-based diet and global phaseout of factory (industrialized animal) farming, the most damaging and prolific form of animal agriculture. The gradual global phaseout of industrialized animal farming can be achieved by increasingly replacing animal meat and other animal products with plant-based products, ending government subsidies for animal-based meat, dairy, and eggs, and initiating taxes on such products. Failure to act will ultimately result in a scenario of irreversible climate change with widespread famine and disease, global devastation, climate refugees, and warfare. We therefore suggest an "All Life" approach, invoking the interconnectedness of all life forms on our planet. The logistics for achieving this include a global standardization of Environmental, Social, and Governance (ESG) or similar measures and the introduction of a regulatory body for verification of such measures. These approaches will help deliver environmental and sustainability benefits for our planet far beyond an immediate reduction in global warming.

Risk Factors and Prediction of Stroke in a Population with High Prevalence of Diabetes: The Strong Heart Study.

BACKGROUND AND OBJECTIVE: American Indians have a high prevalence of diabetes and higher incidence of stroke than that of whites and blacks in the U.S. Stroke risk prediction models based on data from American Indians would be of clinical and public health value. METHODS AND RESULTS: A total of 3483 (2043 women) Strong Heart Study participants free of stroke at baseline were followed from 1989 to 2010 for incident stroke. Overall, 297 stroke cases (179 women) were identified. Cox models with stroke-free time and risk factors recorded at baseline were used to develop stroke risk prediction models. Assessment of the developed stroke risk prediction models regarding discrimination and calibration was performed by an analogous C-statistic (C) and a version of the Hosmer-Lemeshow statistic (HL), respectively, and validated internally through use of Bootstrapping methods. RESULTS: Age, smoking status, alcohol consumption, waist circumference, hypertension status, an-tihypertensive therapy, fasting plasma glucose, diabetes medications, high/low density lipoproteins, urinary albumin/creatinine ratio, history of coronary heart disease/heart failure, atrial fibrillation, or Left ventricular hypertrophy, and parental history of stroke were identified as the significant optimal risk factors for incident stroke. DISCUSSION: The models produced a C = 0.761 and HL = 4.668 (p = 0.792) for women, and a C = 0.765 and HL = 9.171 (p = 0.328) for men, showing good discrimination and calibration. CONCLUSIONS: Our stroke risk prediction models provide a mechanism for stroke risk assessment designed for American Indians. The models may be also useful to other populations with high prevalence of obesity and/or diabetes for screening individuals for risk of incident stroke and designing prevention programs.

Mirror aneurysms: a reflection on natural history.

OBJECT: Investigators conducting the International Study of Unruptured Intracranial Aneurysms, sponsored by the National Institutes of Health, sought to evaluate predictors of future hemorrhage in patients who had unruptured mirror aneurysms. These paired aneurysms in bilateral arterial positions mirror each other; their natural history is unknown. METHODS: Centers in the US, Canada, and Europe enrolled patients for prospective assessment of unruptured intracranial aneurysms. Central radiological review confirmed the presence or absence of mirror aneurysms in patients without a history of prior subarachnoid hemorrhage (SAH) (Group 1). Outcome at 1 and 5 years and aneurysm characteristics are compared. RESULTS: Of 3120 patients with aneurysms treated in 61 centers, 376 (12%) had mirror aneurysms, which are more common in women than men (82% [n = 308] vs 73% [n = 1992], respectively; p <0.001) and in patients with a family history of aneurysm or SAH (p <0.001). Compared with patients with nonmirror saccular aneurysms, a greater percentage of patients with mirror aneurysms had larger (>10 mm) aneurysms (mean maximum diameter 11.7 vs 10.4 mm, respectively; p <0.001). The most common distribution for mirror aneurysms was the middle cerebral artery (34% [126 patients]) followed by noncavernous internal carotid artery (32% [121]), posterior communicating artery (16% [60]), cavernous internal carotid artery (13% [48]), anterior cerebral artery/anterior communicating artery (3% [13]), and vertebrobasilar circulation (2% [8]). When these patients were compared with patients without mirror aneurysms, no statistically significant differences were found in age (mean age 54 years in both groups), blood pressure, smoking history, or cardiac disease. Aneurysm rupture rates were similar (3.0% for patients with mirror aneurysms vs 2.8% for those without). CONCLUSIONS: Overall, patients with mirror aneurysms were more likely to be women, to report a family history of aneurysmal SAH, and to have larger aneurysms. The presence of a mirror aneurysm was not an independent predictor of future SAHs.

Incremental value of biochemical and echocardiographic measures in prediction of ischemic stroke: the Strong Heart Study.

BACKGROUND AND PURPOSE: American Indians have high rates of stroke. Improved risk stratification could enhance prevention, but the ability of biochemical and echocardiographic markers of preclinical disease to improve stroke prediction is not well-defined. METHODS: We evaluated such markers as predictors of ischemic stroke in a community-based cohort of American Indians without prevalent cardiovascular or renal disease. Laboratory markers included C-reactive protein, fibrinogen, urine albumin-to-creatinine ratio, and glycohemoglobin (HbA1c), whereas echocardiographic parameters comprised left atrial diameter, left ventricular mass, mitral annular calcification, and the ratio of early to late mitral diastolic velocities. Predictive performance was judged by indices of discrimination, reclassification, and calibration. RESULTS: After adjustment for standard risk factors, only HbA1c, albuminuria, and left atrial diameter were significantly associated with first ischemic stroke. Addition of HbA1c, although not urine albumin-to-creatinine ratio, to a basic clinical model significantly improved the C-statistic (0.714 versus 0.695; P=0.044), whereas left atrial diameter modestly enhanced integrated discrimination improvement (0.90%; P=0.004), but not the C-statistic (0.701; P=0.528). When combined with HbA1c, left atrial diameter further increased integrated discrimination improvement (1.81%; P<0.001) but not the C-statistic (0.716). No marker achieved significant net reclassification improvement. CONCLUSIONS: In this cohort at high cardiometabolic risk, HbA1c emerged as the foremost predictor of ischemic stroke when added to traditional risk factors, affording substantially improved discrimination, with a more modest contribution for left atrial diameter. These findings bolster the role of HbA1c in cardiovascular risk assessment among persons with glycometabolic disorders and provide impetus for further study of the incremental value of echocardiography in high-risk populations.

Incidence and risk factors for stroke in American Indians: the Strong Heart Study.

BACKGROUND: There are few published data on the incidence of fatal and nonfatal stroke in American Indians. The aims of this observational study were to determine the incidence of stroke and to elucidate stroke risk factors among American Indians. METHODS AND RESULTS: This report is based on 4549 participants aged 45 to 74 years at enrollment in the Strong Heart Study, the largest longitudinal, population-based study of cardiovascular disease and its risk factors in a diverse group of American Indians. At baseline examination in 1989 to 1992, 42 participants (age- and sex-adjusted prevalence proportion 1132/100 000, adjusted to the age and sex distribution of the US adult population in 1990) had prevalent stroke. Through December 2004, 306 (6.8%) of 4507 participants without prior stroke suffered a first stroke at a mean age of 66.5 years. The age- and sex-adjusted incidence was 679/100 000 person-years. Nonhemorrhagic cerebral infarction occurred in 86% of participants with incident strokes; 14% had hemorrhagic stroke. The overall age-adjusted 30-day case-fatality rate from first stroke was 18%, with a 1-year case-fatality rate of 32%. Age, diastolic blood pressure, fasting glucose, hemoglobin A(1c,) smoking, albuminuria, hypertension, prehypertension, and diabetes mellitus were risk factors for incident stroke. CONCLUSIONS: Compared with US white and black populations, American Indians have a higher incidence of stroke. The case-fatality rate for first stroke is also higher in American Indians than in the US white or black population in the same age range. Our findings suggest that blood pressure and glucose control and smoking avoidance may be important avenues for stroke prevention in this population.

Unruptured intracranial aneurysms: natural history and clinical management. Update on the international study of unruptured intracranial aneurysms.

In guiding treatment decisions for all patients with unruptured intracranial aneurysms, it is important to compare size-, site-, and group-specific natural history data with size-, site- and age-specific treatment morbidity and mortality data. Because patient age has a major effect on operative morbidity and mortality, but relatively little effect on natural history, surgical treatment of an UIA patient over age 50 and any treatment of UIA patients over age 70 should be considered with particular vigilance. Optimally, patients should be evaluated and treated at high-volume centers in a setting that emphasizes neurovascular teamwork and unbiased presentation and delivery of different therapeutic option, including the option of observation, which is often appropriate for patients with UIAs.

Population-based study of the relationship between patent foramen ovale and cerebrovascular ischemic events.

OBJECTIVE: To determine whether patent foramen ovale (PFO) is a risk factor for a cryptogenic cerebrovascular ischemic event (CIE). METHODS: This case-control study of 1072 residents of Olmsted County, Minnesota, who underwent contrast transesophageal echocardiography between 1993 and 1997 included 519 controls without CIE randomly selected from the population, 262 controls without CIE referred for transesophageal echocardiography because of cardiac disease, 158 cases with incident CIE of obvious cause (noncryptogenic), and 133 cases with incident CIE of uncertain cause (cryptogenic). RESULTS: Large PFOs were detected in 108 randomly selected controls (20.8%), 22 referred controls (8.4%), 17 noncryptogenic CIE cases (10.8%), and 22 cryptogenic CIE cases (16.5%). After adjustment for age, sex, hypertension, smoking, atrial fibrillation, ischemic heart disease, and number of contrast injections, the presence of a large PFO was not significantly associated with group status (P=.07). Using the odds of the presence of large PFO in the randomly selected controls as the reference, the odds ratio (95% confidence interval) of the presence of large PFO was 0.47 (0.26-0.87) for referred controls, 0.69 (0.37-1.29) for noncryptogenic CIE cases, and 1.10 (0.63-1.90) for cryptogenic CIE cases. CONCLUSIONS: Patent foramen ovale is not a risk factor for cryptogenic ischemic stroke or transient ischemic attack in the general population. The PFO's importance in the genesis of cryptogenic CIE may have been overestimated in previous studies because of selective referral of cases and underascertainment of PFO among comparison groups of patients referred for echocardiography for clinical indications other than cryptogenic CIE.

Population-based study of the relationship between atherosclerotic aortic debris and cerebrovascular ischemic events.

OBJECTIVE: To assess the validity of the suggestion that protruding atheromatous material in the thoracic aorta is an important cause of cerebrovascular ischemic events (CIEs) (ie, transient ischemic attack or ischemic stroke). METHODS: This case-control study of Olmsted County, Minnesota, residents who underwent transesophageal echocardiography (TEE) from 1993 to 1997 included controls without CIE randomly selected from the population, controls without CIE referred for TEE because of cardiac disease, cases with incident CIE of obvious cause (noncryptogenic), and cases with incident CIE of uncertain cause (cryptogenic). RESULTS: Of the 1135 subjects, 520 were randomly selected controls without CIE, 329 were controls without CIE referred for TEE, 159 were noncryptogenic CIE cases, and 127 were cryptogenic CIE cases. Complex atherosclerotic aortic debris in ascending and transverse segments of the arch was detected in 8 randomly selected controls (1.5%), 13 referred controls (4.0%), and 15 noncryptogenic (9.4%) and 4 cryptogenic (3.1%) CIE cases. After adjusting for age, sex, hypertension, smoking, atrial fibrillation, valvular heart disease, congestive heart failure, and atherosclerosis other than in the thoracic aorta, complex atherosclerotic aortic debris was not significantly associated with group status. With randomly selected controls as the referent group, odds ratios (95% confidence intervals) were 1.72 (0.61-4.87) for referred controls, 3.16 (1.18-8.51) for noncryptogenic CIE cases, and 1.39 (0.39-4.88) for cryptogenic CIE cases. CONCLUSIONS: Complex atherosclerotic aortic debris is not a risk factor for cryptogenic ischemic stroke or transient ischemic attack but is a marker for generalized atherosclerosis and well-established atherosclerotic and cardioembolic mechanisms of cerebral ischemia. Embolization from the aorta is not a common mechanism of ischemic stroke or transient ischemic attack.

Patent foramen ovale: innocent or guilty? Evidence from a prospective population-based study.

OBJECTIVES: We sought to determine the association between patent foramen ovale (PFO), atrial septal aneurysm (ASA), and stroke prospectively in a unselected population sample. BACKGROUND: The disputed relationship between PFO and stroke reflects methodologic weaknesses in studies using invalid controls, unblinded transesophageal echocardiography examinations, and data that are unadjusted for age or comorbidity. METHODS: The use of transesophageal echocardiography to identify PFO was performed by a single echocardiographer using standardized definitions in 585 randomly sampled, Olmsted County (Minnesota) subjects age 45 years or older participating in the Stroke Prevention: Assessment of Risk in a Community (SPARC) study. RESULTS: A PFO was identified in 140 (24.3%) subjects and ASA in 11 (1.9%) subjects. Of the 140 subjects with PFO, 6 (4.3%) had an ASA; of the 437 subjects without PFO, 5 had an ASA (1.1%, two-sided Fisher exact test, p = 0.028). During a median follow-up of 5.1 years, cerebrovascular events (cerebrovascular disease-related death, ischemic stroke, transient ischemic attack) occurred in 41 subjects. After adjustment for age and comorbidity, PFO was not a significant independent predictor of stroke (hazard ratio 1.46, 95% confidence interval 0.74 to 2.88, p = 0.28). The risk of a cerebrovascular event among subjects with ASA was nearly four times higher than that in those without ASA (hazard ratio 3.72, 95% confidence interval 0.88 to 15.71, p = 0.074). CONCLUSIONS: These prospective population-based data suggest that, after correction for age and comorbidity, PFO is not an independent risk factor for future cerebrovascular events in the general population. A larger study is required to test the putative stroke risk associated with ASA.

Reprint of: SYMPOSIUM ON CEREBROVASCULAR DISEASES. Pathogenesis, Natural History, and Treatment of Unruptured Intracranial Aneurysms.

Unruptured intracranial aneurysms (UIAs) are a major public health issue. These lesions have become increasingly recognized in recent years with the advent of advanced cerebral imaging techniques. Epidemiological evidence from multiple sources suggests that most intracranial aneurysms do not rupture. Therefore, it is desirable to identify which UIAs are at greatest risk of rupture when considering which to repair. It is important to compare size-, site-, and group-specific natural history rates with size-, site-, and age-specific morbidity and mortality associated with UIA repair because increased natural history risk often is associated with increased risk of aneurysm repair. Patient age is crucial in decision making because of its major effect on operative morbidity and mortality; however, it does not substantially affect natural history. The effect of age is most notable in patients about 50 years of age and older for open surgery and about 70 years of age and older for endovascular procedures. In general, rupture risk is lowest for patients in asymptomatic group 1 (no history of subarachnoid hemorrhage) with UIAs less than 7 mm in diameter in the anterior circulation. Surgical morbidity and mortality are most favorable for asymptomatic patients younger than 50 years who have UIAs less than 24 mm in diameter in the anterior circulation and no history of ischemic cerebrovascular disease. Endovascular morbidity and mortality may be less age dependent, and this could favor endovascular procedures, particularly in patients aged 50 to 70 years. An important issue is determining immediate vs long-term risk regarding treatment effectiveness and durability. This issue emphasizes the importance of long-term follow-up in patients after surgical and endovascular procedures.

Mitral annular calcification, aortic valve sclerosis, and incident stroke in adults free of clinical cardiovascular disease: the Strong Heart Study.

BACKGROUND AND PURPOSE: Mitral annular calcification (MAC) and aortic valve (AV) sclerosis have each been linked to cardiovascular disease. Whether MAC and AV sclerosis are risk factors for stroke independent of other echocardiographic or laboratory predictors has not been established. We evaluated the relationship between MAC, AV sclerosis, and first stroke events in a population-based cohort. METHODS: Our study cohort consisted of 2723 American Indians participating in the Strong Heart Study who were free of prevalent cardiovascular disease. Participants underwent standardized clinical, echocardiographic, and laboratory evaluation, and incident stroke was ascertained using validated methods. RESULTS: During a median follow-up of 7 years, 86 strokes occurred. Age- and sex-adjusted incidence rates of stroke were significantly increased for MAC (rate ratio [RR], 3.12; 95% CI, 1.77 to 5.25) but not for AV sclerosis (RR, 1.15; 95% CI, 0.45 to 2.49). MAC was also associated with a reduced time to first stroke events after adjustment for clinical variables and the inflammatory markers C-reactive protein and fibrinogen (hazard ratio [HR], 2.42; 95% CI, 1.39 to 4.21) or the echocardiographic covariates left ventricular hypertrophy and left atrial enlargement (HR, 1.89; 95% CI, 1.04 to 3.41). Individuals with and without AV sclerosis showed no significant difference in stroke-free survival in unadjusted analyses (P=0.698). Crossing of the survival curves precluded multivariable analysis using Cox models. CONCLUSIONS: In this cohort of American Indians without clinical cardiovascular disease, the presence of MAC, but not AV sclerosis, proved to be a strong risk factor for incident stroke after extensive adjustment for other predictors. Individuals exhibiting MAC may benefit from aggressive risk factor modification, but this will require further investigation.

The natural history of radiographically defined vertebrobasilar nonsaccular intracranial aneurysms.

BACKGROUND: Vertebrobasilar nonsaccular intracranial aneurysms (VBNIA) are characterized by dilatation, elongation, and tortuosity of the vertebrobasilar system. METHODS: The medical records and imaging of patients with vertebrobasilar fusiform aneurysms or dolichoectasia between 1989 and 2001 were reviewed. Prospective follow-up was obtained. RESULTS: One hundred and fifty-nine patients were identified (74% male) with 719 patient years of follow-up. Presenting events included: hemorrhage (3%), ischemia (28%), and compression (22%). The remainder were incidental. The 1-, 5-, and 10-year risk of cerebral infarction (CI) due toVBNIA is 2.7, 11.3, and 15.9% respectively. The risk of recurrent CI is 6.7% per patient year. Median survival was 7.8 years and death was most commonly due to ischemia. CONCLUSIONS: VBNIA are more common in men and typically present in the 6-7th decade. Recurrent CI is more common than hemorrhage risk.

Outcomes among valvular heart disease patients experiencing ischemic stroke or transient ischemic attack in Olmsted County, Minnesota.

OBJECTIVE: To estimate the rates and predictors of survival and recurrence among residents of Olmsted County, Minnesota, who received an Initial diagnosis based on 2-dimensional color Doppler echocardiography of moderate or severe mitral or aortic stenosis or regurgitation and who experienced a first ischemic stroke, transient ischemic attack (TIA), or amaurosis fugax. PATIENTS AND METHODS: At the Mayo Clinic in Rochester, Minn, we used the resources of the Rochester Epidemiology Project to identify Individuals who met the criteria for inclusion in the study and to verify exclusion criteria. The study included all residents of Olmsted County, Minnesota, who experienced a first Ischemic stroke, TIA, or amaurosis fugax within 30 days of or subsequent to receiving a first-time 2-dimensional color Doppler echocardlography-based diagnosis of moderate or severe mitral or aortic stenosis or regurgitation between January 1, 1985, and December 31, 1992. The Kaplan-Meier product-limit method was used to estimate the rates of subsequent stroke and death after the ischemic stroke, TIA, or amaurosis fugax. The Cox proportional hazards model was used to assess the effect of several potential risk factors on subsequent stroke occurrence and death. RESULTS: For the 125 patients in the study, the Kaplan-Meier estimates of the risk of death and the risk of stroke at 2-year follow-up were 38.6% (95% confidence interval [CI], 29.9%-47.5%) and 18.5% (95% CI, 10.0%-27.0%), respectively. Compared with the general population, death rates were significantly Increased (standardized mortality ratio = 1.75; 95% CI, 1.38-2.19; P < .001) but rates of subsequent stroke occurrence were not (standardized morbidity ratio = 1.20; 95% CI, 0.75-1.84; P = .40). After adjustment for age, sex, and cardiac comorbidity, neither the type nor severity of valvular heart disease was an independent determinant of survival or subsequent stroke occurrence. CONCLUSIONS: Patients with mitral or aortic valvular heart disease who experience Ischemic stroke, TIA, or amaurosis fugax have Increased rates of death, but not recurrent stroke, compared with expected rates. Other cardiovascular risk factors are more important determinants of survival In these patients than the type or echocardiographic severity of the valvular heart disease.

Clinical, laboratory, and transesophageal echocardiographic correlates of interatrial septal thickness: a population-based transesophageal echocardiographic study.

BACKGROUND: The determinants of interatrial septal (IAS) thickening ("lipomatous hypertrophy"), a common echocardiographic finding in the elderly, are poorly defined. The objective of this study was to determine the clinical, laboratory, and transesophageal echocardiographic correlates of IAS thickening in the general population. METHODS: The thickness of the IAS was measured by transesophageal echocardiography in 384 patients (median age: 66 years; range: 51-101 years; 53% men) participating in a population-based study (Stroke Prevention: Assessment of Risk in a Community). The associations between atherosclerosis risk factors, clinical cardiovascular disease, aortic atherosclerotic plaques, and IAS thickness were examined. RESULTS: Age and body surface area (BSA) were significantly associated with IAS thickness (median: 6 mm; range: 2-17 mm). IAS thickness increased by 12.6% per 10 years of age (95% confidence interval: 9.0-16.4%) adjusting for sex and BSA, and increased by 7.0% per 0.1 m 2 BSA (confidence interval: 5.0-9.2%) adjusting for age and sex. Overall, age, sex, and BSA accounted for 22.5% of the variability in IAS thickness. Current smoking (20.4% increase in IAS thickness in current smokers) and hypertension treatment (8.5% increase in treated patients) were associated with increased IAS thickness, adjusting for age, sex, and BSA ( P < .05), but these two risk factor variables jointly explained only an additional 2.3% of the variability in IAS thickness beyond the variability explained by age, sex, and BSA. Clinical coronary artery and cerebrovascular disease, atrial arrhythmias, and aortic atherosclerotic plaques were not associated with IAS thickness, adjusting for age, sex, and BSA ( P > .3). CONCLUSIONS: IAS thickening is an age-associated process. Atherosclerosis risk factors are weakly associated with IAS thickening, whereas atherosclerotic vascular disease is not.